The present invention relates generally to carrier matrices for demineralized bone matrix and more particularly, to polyethylene oxide carrier matrices for demineralized bone matrix.
Demineralized bone matrix (DBM) is an effective substitute for autologous bone graft because it is both osteoinductive and osteoconductive. However, in the dry powder form, demineralized bone matrix powder is not easy to handle during surgery. For this reason, many different formulations and forms of demineralized bone matrix have been developed for the purpose of improving handling during surgery. Most of these formulations combine the DBM with a carrier that serves to bind the DBM particles together to form a paste or putty. Typical carriers are glycerol, polysaccharide solutions such as hyaluronic acid, lecithin, and gelatin. One problem with these puffy and paste formulations is that they remain malleable after implantation, and thereby can deform if subjected to compressive forces. One particular procedure in which bone grafts are subjected to compressive forces is postero-lateral spine fusions.
Another DBM-containing formulation having the property of macroscopic cohesiveness, as described above, can be produced by embedding DBM in a carrier matrix which is then be crosslinked with covalent intermolecular bonds. Such a crosslinked carrier would resist the drawbacks of uncrosslinked carriers, namely dissolving and deforming in vivo. However, most common crosslinking methods cannot be used without inactivating the bioactivity of the DBM. For instance, most chemical crosslinking agents, such as formaldehyde, glutaraldehyde, carbodiimides (e.g. 1 -Ethyl-3-[3-dimethylaminopropyl]-carbodiimide hydrochloride) may crosslink protein carrier-matrices such as gelatin and collagen, but these chemical agents also interact with and deactivate the bioactive factors contained in the DBM such as bone morphogenic proteins. Another standard crosslinking technology, dehydrothermal crosslinking, is carried out at temperatures of 100° C. to 200° C., well above the temperature at which most proteins are denatured, including the bioactive components within the DBM.
As can be seen, there is a need for a carrier/matrix for active (osteoinductive) DBM which has macroscopic cohesiveness such that it does not dissolve, fall apart, or significantly deform in aqueous solutions or under mild compressive forces.